Total Venous Occlusion Research Articles

Effect of platelet glycoprotein IIb/IIIa receptor antagonist on survival of epigastric island flaps in rats with total venous occlusions

We evaluated the effect of tirofiban hydrochloride on the survival of epigastric island flaps in rats that had had all the veins occluded. Male Wistar Albino rats were randomly assigned to control (treated with sterile saline) and experimental (treated with tirofiban hydrochloride 1 mg/kg intravenously) groups. An epigastric island skin flap 3x6 cm was raised in each rat. All veins that drained the flap were ligated to give total venous occlusion. Blood flow was recorded by laser Doppler preoperatively (baseline), immediately after the flap had been sutured back to its original position (acute) and on postoperative days 1 and 3. The degree of necrosis was evaluated on day 3. Mean percentage necrosis and minimum laser Doppler values were compared in the two groups. Total necrosis was evident on day 1 in the control group and on day 3 in the experimental group. Macroscopic evidence was confirmed by histopathological examination. There were appreciable differences in blood flow and in the necrotic area of the flap in the experimental group compared with the control group on both days 1 and 3. Tirofiban hydrochloride might be effective in this flap model.

Successful coronary sinus lead replacement despite total venous occlusion using femoral pull through, two operator counter-traction and subclavian venoplasty

The majority of patients presenting for lead extraction have indications for a replacement lead. Venous stenosis is common in recipients of pacing leads and can impede ipsilateral lead replacement. Recanalization through an existing tract after lead extraction allows successful lead placement but may require complex hybrid lead extraction and revascularization techniques. We present a case in which a combination of femoral lead extraction with complete guidewire pull-through, two operator external counter-traction and subclavian venoplasty was used to successfully replace a coronary sinus lead in a patient with total subclavian venous occlusion.

Protective Effects of Monoclonal Antibody to Intercellular Adhesion Molecule-1 in Venous Ischemia-Reperfusion Injury: Experimental Study in Rats

Flaps with venous occlusion have a decreased survival rate compared with arterial occlusion. It seems that several factors are involved in the etiology of total venous occlusion, including free radicals, edema, thrombosis, and reperfusion injury. In the present study, the authors evaluated the blockage of polymorphonuclear leukocyte endothelial adhesion by using a monoclonal antibody to the intercellular adhesion molecule 1 (ICAM-1) ligand to prevent venous ischemia-reperfusion injury in rat epigastric island flaps. A skin flap (3 x 4 cm) supplied by the superficial epigastric artery and vein was harvested unilaterally in 40 male Wistar rats. Total venous occlusion of the skin flap was achieved. Arterial inflow was left intact. Rats were randomly divided into four groups (n = 10). In Group 1; rats were intravenously pretreated with 0.5 ml of 0.9 percent normal saline 15 min before applying a venous clamp, and the flaps were subjected to 6 hr of venous ischemia. In Group 2; rats were intravenously pretreated with 0.05 mg of monoclonal antibody to the intercellular adhesion molecule 1 (0.20 mg/kg) in 0.5 ml of 0.9 percent normal saline 15 min before applying the venous clamp, and the flaps were subjected to venous ischemia as in Group 1. In Group 3; rats were pretreated as in Group 1, and the flaps were subjected to 8 hr of venous ischemia. In Group 4; rats were pretreated as in Group 2, and the flaps were subjected to 8 hr of venous ischemia. The flaps were assessed histologically and by measuring viable and non-viable areas on postoperative day 7. Flap measurements revealed that blocking the action of ICAM-1 IN VIVO by administering monoclonal antibody significantly attenuated ischemic injury after 6 or 8 hr of venous occlusion.

Influence of Angiotensin Converting Enzyme Insertion/Deletion Polymorphism on Long-term Total Graft Occlusion after Coronary Artery Bypass Surgery

The renin-angiotensin system has a very important role in coronary thrombosis and restenosis. Plasma angiotensin converting enzyme (ACE) activity is associated with an insertion/deletion polymorphism in the gene coding for ACE. It is known that there is a strong correlation between ACE DD and atherosclerosis. However, little has been documented about its role in venous graft failure. The objective of this study was to investigate the relationships among the ACE gen polymorphism and long-term vein graft occlusion. The study population consisted of 87 consecutive white patients with symptomatic coronary artery disease in the previous month, who had had aorto-coronary bypass surgery (ACBS) more than 5 years back and who underwent coronary angiography for diagnostic purposes. On the same day of angiography, 10 mL whole blood was taken for ACE gene insertion/deletion (I/D) polymorphism. Mean age of the patients was 64.4 +/- 8.6 years, and 71 (82%) of the patients were men. The average ACBS time was 7.9 +/- 1.9 years. The ACE genotype was II in 15 patients (17.2%), ID in 47 patients (54.0%), and DD in 25 patients (28.7%). Thus, D allele frequency was .82. There was no significant difference between the cases with regard to age, body mass index, blood pressure status, plasma glucose level, plasma lipid profile, smoking status, average of ACBS time or family history of coronary heart disease. In ACE II group 5 patients had total venous graft occlusion, in ACE ID group 27 patients had total occlusion and in ACE DD group 20 patients had at least one graft total occlusion. The frequency of the venous graft occlusion about total venous grafts is 36% in the ACE II group, 49% in the ACE ID group, and 80% in the ACE DD group (P = .01). The ACE I/D gene polymorphism is associated with long-term survival of venous conduit. The ACE DD genotype or D allele influences the angiographic outcome of patients post-ACBS. These data suggest that routine determination of the ACE genotype may help identify patients who are at higher risk of venous graft failure after ACBS.

Placement of Transvenous Pacemaker and ICD Leads Across Total Chronic Occlusions

To establish a method of implantation for device leads across total venous occlusions. Indications for pacemaker and implantable cardiac defibrillator implantation continue to expand. Chronic venous occlusions are increasingly encountered with lead placement. Some degree of obstruction can be as high as 13% before device implantation and 50% after transvenous device implantation. We report an approach of venoplasty/dilatation of chronic total occlusions to allow lead placement. From January 1, 2002 through December 16, 2004, 1,356 systems (initial and upgrade) were implanted at the University of Virginia. At the time of device implant, seven patients were noted to have chronic venous occlusions and alternative access was precluded. Four of the seven patients had an existing system; the other three received initial implantations. Subsequently, these seven patients had a 5 Fr catheter placed in the basilic/axillary/subclavian vein and a venogram was obtained to demonstrate the area of chronic occlusion. A guide wire was advanced across the lesion for initial recanalization. Dilatation or venoplasty was performed at the occluded site. A guide wire was retained across the lesion and the patient underwent lead implantation. In all seven patients, recanalization was achieved and leads were successfully placed. There were no complications or damage to the vessels or existing leads. Venoplasty or dilatation of chronic total venous occlusion is a safe and effective technique, which allows for placement of transvenous leads.

Effect of the delay phenomenon on survival of rat island skin flaps with total venous occlusion.

Necrosis is an inevitable result in flaps with total venous occlusion even if arterial flow is sufficient. The purpose of this study was to investigate the effect of surgical delay on rat island skin flaps with total venous occlusion, using 20 Swiss albino rats. Two epigastric island flaps were elevated in each rat. Flaps of experimental and control groups were elevated in the same animal. In the experimental group (n=20), flap boundaries were incised down to the fascia and the incisions were sutured as a delay procedure at the first stage. After 7 days, the 3 x 6-cm epigastric island flap was elevated, the inferior epigastric vein was ligated, and was cut under X60 magnification. Then, all flaps were sutured back to their original beds. In the control group (n=20), the same surgical procedure as in the experimental group was repeated without a delay procedure. Viability was assessed at postoperative days 1, 3, and 7. At the end of day 7, all flaps in the control group were totally necrosed; however flaps in the experimental group survived partially. The surviving area ranged between 24 and 74 percent (mean: 60 +/- 15 percent). The differences between the two groups were found to be statistically significant, using Student's t-test ( p<0.005). Surgical delay could not completely save a flap with totally interrupted venous return. Nevertheless, a 60 +/- 15 percent portion of these flaps could survive with the help of a simple delay procedure.

Effect of total venous occlusion on capillary flow and necrosis in skeletal muscle.

Limb replantation and microvascular transfer of flaps are sometimes complicated by postoperative venous thrombosis. Total venous occlusion can lead to complete shutdown of microvascular perfusion, resulting in failure of the transfer or replantation. Once venous return stops, it must be restored within a critical period of time for tissue survival. The purpose of this experiment was to delineate this critical period of time at which no reflow and irreversible muscle necrosis occurs by the use of a rat gracilis flap microcirculation model. The gracilis muscle of 40 male Wistar rats (135.3 +/- 37.2 g) was elevated on its vascular pedicle and mounted on a raised platform for videomicroscopic analysis. Animals were randomly assigned to one of four groups: (1) sham (no total venous occlusion), (2) 10 minutes of total venous occlusion, (3) 30 minutes of total venous occlusion, and (4) 60 minutes of total venous occlusion. Total venous occlusion was established by placing a microvascular clamp across the femoral vein at the junction of the gracilis pedicle. The number of flowing capillaries in five consecutive high-power fields (832x) were counted at baseline and at 5, 15, 30, 60, 120, 180 minutes, and 24 hours after reperfusion. At 24 hours after reperfusion, the gracilis muscles were harvested and stained with nitroblue tetrazolium. Percentage of muscle necrosis was measured by using computer planimetry. The data were reported as mean +/- standard error of mean and were compared between groups by analysis of variance and appropriate post hoc comparisons. Total venous occlusion for 10, 30, and 60 minutes showed a significant decrease in the number of flowing capillaries through 24-hour postreversal. There was a significant drop (p < 0.01) in the number of flowing capillaries from 30 minutes of total venous occlusion to 60 minutes of total venous occlusion at all times. Muscle necrosis was significantly increased in all three groups of total venous occlusion compared with the sham group (36.1 +/- 1.7 percent, 45.5 +/- 3.4 percent, 74.1 +/- 4.7 percent versus 14.3 +/- 1.7 percent, and p < 0.01). These results indicate that irreversible tissue damage occurs in a very short time interval (60 minutes) in this model, making the early detection of venous occlusion critical to the successful correction of this complication.

Effect of Hyperbaric Oxygen and Medicinal Leeching on Survival of Axial Skin Flaps Subjected to Total Venous Occlusion

This study evaluates the effect of hyperbaric oxygen and medicinal leeching on axial skin flaps subjected to total venous occlusion. Axial epigastric skin flaps (3 × 6 cm) were elevated on their vascular pedicles in 40 male Wistar rats. Total venous occlusion was achieved by division of all veins draining the skin flap. Arterial inflow was left intact. Animals were randomly assigned to one of five groups: sham (n = 8); control, total venous occlusion only (n = 8); occlusion with hyperbaric oxygen (n = 8); occlusion with leeching (n = 8); occlusion with leeching and hyperbaric oxygen (n = 8). The hyperbaric oxygen protocol consisted of 90-minute treatments, twice daily, with 100% O2 at 2.5 atmospheres absolute for 4 days. The leeching protocol consisted of placing medicinal leeches on the congested flaps for 15 minutes, once daily, for 4 days. Laser Doppler measurements of flap perfusion were recorded preoperatively, postoperatively, and on postoperative days 1 and 3. The percentage of flap necrosis was evaluated on postoperative day 3. Mean percentage necrosis and mean laser Doppler readings were compared between both groups. The flaps in the sham group demonstrated 99 percent survival, whereas the flaps in the occlusion-only group demonstrated 100 percent necrosis. The flaps in the occlusion with oxygen, the occlusion with leeching, and the occlusion with oxygen and leeching groups demonstrated 1, 25, and 67 percent survival, respectively. Sham laser Doppler readings remained within normal limits. Laser Doppler readings in the occlusiononly and the occlusion with oxygen groups decreased to negligible levels on postoperative day 1, and on postoperative day 3 no perfusion was demonstrated. In both the occlusion with leeching and the occlusion with leeching and oxygen groups, there was also a significant decrease in laser Doppler measurements after surgery, but perfusion remained stable throughout the remainder of the study. This study demonstrates that hyperbaric oxygen alone is not an effective treatment for skin flaps compromised by total venous occlusion. The combination of leeching and hyperbaric oxygen treatment of total venous occlusion results in a significant increase in flap survival above that found with leeching alone. It appears that hyperbaric oxygen is effective because of the venous outflow provided by leeching as demonstrated by laser Doppler flow readings. (Plast. Reconstr. Surg. 104: 1029, 1999.)

Effect of hyperbaric oxygen and medicinal leeching on survival of axial skin flaps subjected to total venous occlusion.

This study evaluates the effect of hyperbaric oxygen and medicinal leeching on axial skin flaps subjected to total venous occlusion. Axial epigastric skin flaps (3 x 6 cm) were elevated on their vascular pedicles in 40 male Wistar rats. Total venous occlusion was achieved by division of all veins draining the skin flap. Arterial inflow was left intact. Animals were randomly assigned to one of five groups: sham (n = 8); control, total venous occlusion only (n = 8); occlusion with hyperbaric oxygen (n = 8); occlusion with leeching (n = 8); occlusion with leeching and hyperbaric oxygen (n = 8). The hyperbaric oxygen protocol consisted of 90-minute treatments, twice daily, with 100% O2 at 2.5 atmospheres absolute for 4 days. The leeching protocol consisted of placing medicinal leeches on the congested flaps for 15 minutes, once daily, for 4 days. Laser Doppler measurements of flap perfusion were recorded preoperatively, postoperatively, and on postoperative days 1 and 3. The percentage of flap necrosis was evaluated on postoperative day 3. Mean percentage necrosis and mean laser Doppler readings were compared between both groups. The flaps in the sham group demonstrated 99 percent survival, whereas the flaps in the occlusion-only group demonstrated 100 percent necrosis. The flaps in the occlusion with oxygen, the occlusion with leeching, and the occlusion with oxygen and leeching groups demonstrated 1, 25, and 67 percent survival, respectively. Sham laser Doppler readings remained within normal limits. Laser Doppler readings in the occlusion-only and the occlusion with oxygen groups decreased to negligible levels on postoperative day 1, and on postoperative day 3 no perfusion was demonstrated. In both the occlusion with leeching and the occlusion with leeching and oxygen groups, there was also a significant decrease in laser Doppler measurements after surgery, but perfusion remained stable throughout the remainder of the study. This study demonstrates that hyperbaric oxygen alone is not an effective treatment for skin flaps compromised by total venous occlusion. The combination of leeching and hyperbaric oxygen treatment of total venous occlusion results in a significant increase in flap survival above that found with leeching alone. It appears that hyperbaric oxygen is effective because of the venous outflow provided by leeching as demonstrated by laser Doppler flow readings.

Extraction and replacement of permanent pacemaker leads through occluded vessels: use of extraction sheaths as conduits--balloon venoplasty as an adjunct.

Patients (pts) may present for lead extraction with symptomatic or asymptomatic subclavian vein or superior vena cava thrombosis. Replacement of permanent pacemaker leads (PPLs) in these pts may be difficult and may require accessing a new site. We examined the utility of replacing PPLs through completely occluded vessels using extraction sheaths as conduits through the total occlusion. Over six years, a total of 210 atrial and/or ventricular PPLs were extracted from 137 pts. Two pts presented with angiographically documented thrombotic occlusion of the subclavian vein. One additional pt. who had presented with a superior vena cava (SVC) syndrome, had a totally occluded innominate vein and SVC occlusion. Balloon venoplasty was used as an adjunct to dilate the SVC. In all pts, after PPLs were removed via a subclavian extraction sheath through the occluded vessel, the retained sheath was used to place a guide wire, then a peel away dilating sheath, to insert new PPLs, in each case on the side of total venous occlusion. Seven PPLs and two lead fragments were extracted, and five new PPLs replaced, ipsilateral to the venous occlusion. These data show that extraction of PPLs through thrombosed veins may be performed successfully and may not require replacing the leads through a new site. This technique spares the pt the need to access the opposite subclavian vein, and it avoids an excessive number of PPLs in the subclavian vein and SVC. The procedure illustrates an efficient means to reintroduce new PPLs with the potential to reduce associated morbidity, since repeat puncture of the subclavian vein is not required. Safety of the procedure as a whole must be considered with regard to the known risks of lead extraction, some complications of which may be substantial using current techniques.

The effect of mannitol and anisodamin on the prevention of free radical injury to post-ischaemia flaps: an experimental study

Rat abdominal skin flaps were subjected to total venous occlusion for 8 h. Five minutes before release of the vascular occlusion, mannitol, mannitol plus anisodamin, anisodamin or placebo (0.9% normal saline) was administered intravenously. Drug treated flaps showed a statistically significant increase in the proportion of area surviving (P < 0.001). The combination of mannitol and anisodamin was not more effective than either agent alone in increasing the proportion of area surviving. The results of biochemical analyses indicated that neither mannitol nor anisodamin affected xanthine oxidase activity (p > 0.05) but that both agents significantly reduced the increase of malondialdehyde (MDA) concentration caused by ischaemia-reperfusion (p < 0.01). Treatment with mannitol or anisodamin also prevented the increase of lactate and water content and the decrease in glucose content in the island skin flap tissue which occurred on reperfusion. The data indicate that mannitol and/or anisodamin have the potential to salvage anticipated flap necrosis. It is possible that the mechanism of action is inhibition of damage caused by toxic oxygen species and improvement in capillary reperfusion.

Beta-adrenergic stimulation of energy expenditure and forearm skeletal muscle metabolism in lean and obese men

The effect of beta-adrenergic stimulation on whole body energy expenditure and forearm skeletal muscle metabolism was investigated in lean and obese men. Whole body energy expenditure was determined during rest and during intravenous infusion of increasing doses of the nonselective beta-agonist isoprenaline (Iso). Forearm skeletal muscle metabolism was investigated with Iso infusion with and without simultaneous infusion of the beta 1-blocker atenolol (AT) by measuring skeletal muscle blood flow (SMBF) and arteriovenous concentration differences of various metabolites. The changes in SMBF were estimated from forearm total (venous occlusion plethysmography), skin (laser doppler), and fat tissue blood flow (133Xe washout). The increase in whole body energy expenditure with Iso was similar in lean and obese subjects. With Iso, the rise in arterial or arterialized glycerol and nonesterified fatty acids (NEFA) was lower in obese than lean subjects, which may reflect a lower beta-adrenergically mediated lipolysis in obesity. During infusion of increasing doses of Iso, the respiratory exchange ratio decreased significantly in lean subjects but not in the obese subjects, which indicates a more pronounced increase in fat oxidation in lean subjects. This is confirmed by the data on skeletal muscle metabolism, where NEFA uptake was increased in lean subjects, whereas the obese subjects showed a tendency toward an increased glucose uptake and a significantly increased lactate release. With Iso plus AT (mainly beta 2-adrenergic stimulation), both groups showed an increased skeletal muscle lactate release. In conclusion, although the thermogenic response to Iso was similar in lean and obese subjects, the utilization of fat seems to be impaired in obesity.

Total venous inflow occlusion in the normothermic dog: a study of haemodynamic, metabolic and neurological consequences

The acute haemodynamic and metabolic repercussions of total venous inflow occlusion were evaluated in six normal dogs, each of which underwent two four minute occlusions and one eight minute occlusion at normothermia. A further three dogs underwent a single eight minute period of occlusion and were allowed to recover from anaesthesia. Total venous inflow occlusion was well tolerated by all animals. They remained in sinus rhythm at the completion of occlusion, and unassisted haemodynamic recovery occurred rapidly. Recovery was quicker after four minutes than after eight minutes. There was no clinically detectable neurological impairment in three dogs which were allowed to recover.

Real time multivariable laser Doppler analysis of arterial and venous compromise

Laser Doppler perfusion monitoring was used to assess microcirculatory blood flow, volume, and velocity before and after total arterial or total venous occlusion in 18 buttock island flaps. Critical analysis of these three laser Doppler perfusion values was found to be useful in differentiating adequately perfused skin from inadequately perfused skin, as well as in distinguishing arterial from venous compromise. Multivariable laser Doppler analysis demonstrated that arterial occlusion produced a more rapid and greater percentage decrease in flow and volume values than did venous occlusion. Arterial occlusion produced an insignificant percentage change in velocity values, whereas venous occlusion produced a substantial percentage decrease in velocity values. The substantial intrasubject and intersubject variability in absolute laser Doppler perfusion values suggests that normalized or percentage change values are more revealing than absolute values, although they require the acquisition of reliable baseline data.

Effects of Superoxide Dismutase and Allopurinol on the Survival of Acute Island Skin Flaps

We have demonstrated previously that oxygen-derived free radicals are important mediators of tissue injury following ischemia (total venous occlusion) and reperfusion in small (3 cm X 6 cm) island skin flaps in rats. In this study, we evaluated extension of this concept to regional ischemia in large (8 cm X 8 cm) acute island skin flaps which were constructed to exceed their sole blood supply via unilateral inferior epigastric vessels. Under normal (control) circumstances, a significant portion of the flap would undergo necrosis at the periphery, mimicking the corresponding clinical situation. Blocking the generation of superoxide radicals from xanthine oxidase with a single dose of allopurinol prior to flap elevation significantly improved the area of flap viability from 34 +/- 12% to 57 +/- 6% (p less than 0.01) in the random portion of the flap, contralateral to the source of blood supply. Similarly, the detoxification of superoxide radicals with a single dose of superoxide dismutase improved viability from 41 +/- 6% to 58 +/- 7% (p less than 0.01). Similar results were obtained when either of these agents were administered 60 minutes after flap elevation. These findings suggest that oxygen-derived free radicals play an important role in the development of tissue necrosis in the critical transition zone between well-vascularized and devascularized skin.

The influence of venous occlusion on xenon 133 muscle clearance.

Progressive degrees of venous occlusion in the canine hind limb were employed to evaluate the influence of venous disease on the xenon 133 muscle washout test. Increasing degrees of venous occlusion, from superficial venous occlusion alone to total occlusion induced with intravenously administered thrombin, decreased both resting muscle blood flow and maximal muscle blood flow stimulated with intra-arterially administered papaverine hydrochloride. This alteration lasted for varying lengths of time with all but the group with total venous occlusion eventually returning to a normal flow. The status of the venous circulation must be considered in order to accurately interpret the results of the 133Xe clearance test when used to evaluate arterial occlusive disease. The 133Xe washout test may be an accurate indicator of venous occlusion in a limb with normal arterial supply.